1. Technical Field
This invention relates to methods and apparatuses used for dissolving and mixing reagents in liquids, particularly mixing of small volumes in enclosed chambers.
2. Background
An increasing number of chemical and biochemical assays are being carried out in very small chambers. This is especially true for diagnostic assays where small samples are preferred. In many cases solvents and reagents are mixed and a reaction is carried out in a cuvette in which an optical measurement will be made at a later time. The cuvette is inserted into an apparatus such as a spectrophotometer including one or more optical paths in which sample or reference materials are inserted in order that the light absorption characteristics of the reaction products can be evaluated. The cuvette comprises a small rectangular or other-shaped container having opposed sides which are relatively transparent to the wavelengths of light being utilized during analysis.
Although the extent of mixing required depends on the nature of the sample being analyzed and the reagents present, some mixing must occur within the cuvette before reaction between the sample and reagents can take place. Motor-driven paddles can be used if the cuvette is open but not if the cuvette is closed. One common arrangement for mixing involves the use of so-called magnetic stirrers. In this well known arrangement, a magnetically responsive agitator is positioned in a cuvette or other container and is caused to rotate in the presence of an externally applied rotating magnetic field. Typically, the rotating magnetic field is provided by a bar magnet which is mounted beneath the container and rotates about a vertical axis so that the magnetic poles of the bar magnet rotate in a horizontal plane. In this arrangement the magnetic stirring body is itself rotatable in a horizontal plane around a vertical axis and includes permanent or induced magnetic poles spaced apart from its vertical axis.
Magnetic stirring as described above is typically carried out in round containers or containers characterized by a substantially square internal cross section. U.S. Pat. No. 3,997,272 indicates that such magnetic stirrers have been found to be relatively unacceptable in those instances where the internal cross section of the cell departs significantly from a square or circle. Cylindrical stirrers rotating about a horizontal axis in the presence of a horizontally or vertically rotating magnetic field are said to be more efficacious in rectangular cells. Numerous other publications describe magnetically controlled mixers of various types and motions, most of which sweep out relatively large volumes of the chamber in which they are contained.
In most cases, the previously known mixing bodies are not designed for use in a substantially closed container in which any liquid present is constrained on all sides by the walls of the chamber but are rather designed for vessels open to the external environment on one side (generally the top). Furthermore, little attention has been given to problems that arise when measurements are made in a chamber that initially contains a dried reagent that might be dislodged by accidental contact with the mixing body such as during transport or handling. Problems are compounded in situations in which the dried reagent is difficult to dissolve, must be uniformly dissolved, or must be uniformly suspended (e.g., for particulate reagents, such as latex agglutination reagents). Accordingly, there remains a need for improved mixing systems for small enclosed liquid samples.